Ovarian cancer is the most lethal of the gynecological malignancies and the 5th leading cause of cancer death in women. The etiology of ovarian cancer is poorly understood and there are no suitable early detection markers. Due to the late stage at which the disease is usually diagnosed the survival rate is very low and conventional treatment modalities or intervention strategies are usually ineffective. A diet which is high in meats and low in vegetables may be correlated with increased ovarian cancer incidence. An imbalance of omega 3 (OM-3FA) and omega 6 (OM-6FA) fatty acids contributes to excess cancer risk. Studies indicate that populations that consume high amounts of OM-3FA have lower incidences of breast, prostate and colon cancers than do those that consume less OM-3FA. Thus increasing the consumption of OM-3FA may be a nontoxic way to prevent ovarian cancer, augment cancer therapy and to significantly increase life span. Fish oil is an excellent source of long chain OM-3FA which have been shown to have anti-proliferative and pro-apoptotic activities in certain cancers. An effective treatment or dietary intervention that significantly reduces the progression of ovarian cancer has the potential for turning ovarian cancer into a disease that women die WITH not from. The proposed studies will test the effectiveness of a fish oil supplemented diet in the suppression and prevention of ovarian cancer, and examine the mechanism of action of omega-3 fatty acids using the laying hen as a model of ovarian carcinoma. With the exception of the aging hen, there are no other animal models of spontaneous epithelial ovarian cancer that mimic the human disease. We hypothesize that a fish oil supplemented diet will cause a significant reduction in the incidence and severity of ovarian carcinoma in the laying hen. Identification of molecular targets whose expression is affected by fish oil will provide insight into the mechanism of action of omega-3 fatty acids, and may provide new understanding to the etiology of ovarian cancer. These studies will provide the foundation for developing functional food based dietary intervention for the prevention and treatment of ovarian cancer in women. Two Specific Aims are proposed based on the innovative use of the laying hen model of ovarian cancer: Aim 1) to determine the optimum dose of fish oil by assessing the effects on surrogate endpoints in hens;Aim 2) to determine the effect of the optimal dose of fish oil on the suppression and prevention of ovarian cancer in old laying hens prone to high prevalence of cancer. PUBLIC HEALTH RELEVANCE: Research into ovarian cancer, a highly lethal disease, has been limited by the lack of suitable animal models, because, with the exception of the laying hen, no other animals are inflicted with the same type of ovarian cancer that affects women. Using the hen as our model we will investigate the fish oil supplemented diet as a way to prevent and suppress ovarian cancer.